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Neurotransmitters present in intestines affect the brain

Serotonin is not synthesized in the absence of intestinal bacteria

Here is an explanation about the relationship between intestinal bacteria and serotonin. Recent studies have shown that certain types of microorganisms present in the gut microbiota promote the synthesis of serotonin by stimulating endocrine cells of the intestines (*1). On the other hand, the volume of serotonin synthesis in the intestines of germ-free mice drastically decreases. As this result shows, the presence of intestinal bacteria plays an essential role in a proper synthesis of serotonin in the intestines. Once serotonin is synthesized in the intestines, our bodies detect this increase in the production of serotonin. As a result, blood platelets and whole circulatory organs take in the serotonin and the body can provide various physiological functions.

The relationship between the intestine and the brain is called “brain-gut interaction”. It is not yet clearly understood how the serotonin that is synthesized in the intestines affects the brain. However, a scientific experiment with mice has reported that certain intestinal bacteria synthesize short chain fatty acids (mainly butyrate), which promote the synthesis of serotonin in the intestines. This serotonin synthesized in the intestines enters the blood vessels and is taken up by blood platelets to circulate throughout the body. During this process, it stimulates the peripheral nervous system which in turn affects the nerves. Since this peripheral nervous system extends to the brain, scientists infer that serotonin indirectly affects gene expression in the brain and behavioral patterns. In fact, the reduction of serotonin in the brain of germ-free mice has been reported (*2).

Beware of kynurenine which inhibits the function of serotonin

Serotonin is synthesized from tryptophan. However, not only serotonin is synthesized from tryptophan, more than 90% of tryptophan is converted into a component called “kynurenine”. Experts have pointed out that the excessive synthesis of kynurenine can inhibit neurotransmission that raises the risks of developing depressive symptoms. The study about the concentration of tryptophan in the blood among patients with depression have found that the level of tryptophan was low among then. This is probably due to the low amount of tryptophan taken from diet or the fact that tryptophan is excessively converted to kynurenine.

It is important to avoid an excessive conversion of tryptophan to kynurenine in order to have a proper synthesis of serotonin from tryptophan. Kynurenine is more actively synthesized when the body is under an inflammatory condition. Therefore, when we discuss serotonin, it is necessary to cover “anti-inflammation” at the same time. Soybean-based fermented foods, polyamines and short-chain fatty acids which are synthesized by intestinal bacteria have anti-inflammatory effects.

Kynurenine is also synthesized when people are under stress. The experiment using mice has demonstrated that exercise is effective to remove kynurenine. Through the experiment, researchers considered that the normalized metabolism of tryptophan can be a factor of reducing depressive symptoms by doing exercise (* 3).

There are various approaches to achieve the proper synthesis of serotonin in the brain. Here are the summary of the main points. I hope these can be helpful for you.

    • Ingest tryptophan from your daily diet as a raw material of serotonin
    • Ingest magnesium, niacin, folic acid, iron and vitamin B6 in order to activate the enzymes that are involved in the synthesis of serotonin.
    • Ingest an adequate sugar level and activate the secretion of insulin in order to absorb BCAA, which competes with tryptophan, in the muscles.
    • Regulate the bacterial balance in intestines. Ingest dietary fiber, especially indigestible components, in order  to activate bacteria especially the type that synthesizes butyrate.
    • Keep anti-inflammation in mind and proactively eat fermented foods
    • Do adequate exercise to remove the kynurenine that is accumulated by stress.

    Credit to:  Muneaki Takahata Ph.,D.


    *1 Cell. 161, 264-276 (2015) http://www.cell.com/abstract/S0092-8674(15)00248-2

    *2 Cell Host Microbe. 17, 565-576 (2015) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442490/

    *3 Cell. 159, 33-45 (2014) http://www.cell.com/cell/abstract/S0092-8674(14)01049-6